Despite 10 years of intensive research into computer-assisted method development for HPLC separation, relatively few chromatographers use these techniques to a significant extent. We propose to develop a computer program (MOSES - Modular Optimization Software/Expert System) that addresses this problem. Computer-simulation modules based on chromatographic theory will be integrated into an expert system framework that addresses most of the problems encountered during HPLC method development. The program will be applicable to both small-molecule samples (which most previous work addresses) and to large biomolecules of interest in the life sciences. The program will also assist in the selection of initial conditions, sample pretreatment, optimizing the separation and scaling up for preparative separation. Previously recognized needs in computer-assisted method development (e.g., user-friendly environment, reliable and convenient mapping of separation, peak tracking, etc.) will be addressed.